Gelatin/Collagen-based matrix and reservoir nanoparticles require crosslinkers to stabilize the formed
nanosuspensions, considering that physical instability is the main challenge of nanoparticulate systems.
The use of crosslinkers improves the physical integrity of nanoformulations under the-host environment.
Aldehyde-based fixatives, such as formaldehyde and glutaraldehyde, have been widely applied to the
crosslinking process of polymeric nanoparticles. However, their potential toxicity towards human beings
has been demonstrated in many previous studies. In order to tackle this problem, d-glucose was used
during nanoparticle formation to stabilize the gelatin/collagen-based matrix wall and reservoir wall for
the deliveries of Calendula officinalis powder and oil, respectively. In addition, therapeutic selectivity
between malignant and normal cells could be observed. The C. officinalis powder loaded nanoparticles
significantly strengthened the anti-cancer effect towards human breast adenocarcinoma MCF7 cells and
human hepatoma SKHep1 cells when compared with the free powder. On the contrary, the nanoparticles
did not show significant cytotoxicity towards normal esophageal epithelial NE3 cells and human skin
keratinocyte HaCaT cells. On the basis of these evidences, d-glucose modified gelatin/collagen matrix
nanoparticles containing C. officinalis powder might be proposed as a safer alternative vehicle for anticancer
treatments.

Gelatin/Collagen-based matrix and reservoir nanoparticles require crosslinkers to stabilize the formed
nanosuspensions, considering that physical instability is the main challenge of nanoparticulate systems.
The use of crosslinkers improves the physical integrity of nanoformulations under the-host environment.
Aldehyde-based fixatives, such as formaldehyde and glutaraldehyde, have been widely applied to the
crosslinking process of polymeric nanoparticles. However, their potential toxicity towards human beings
has been demonstrated in many previous studies. In order to tackle this problem, d-glucose was used
during nanoparticle formation to stabilize the gelatin/collagen-based matrix wall and reservoir wall for
the deliveries of Calendula officinalis powder and oil, respectively. In addition, therapeutic selectivity
between malignant and normal cells could be observed. The C. officinalis powder loaded nanoparticles
significantly strengthened the anti-cancer effect towards human breast adenocarcinoma MCF7 cells and
human hepatoma SKHep1 cells when compared with the free powder. On the contrary, the nanoparticles
did not show significant cytotoxicity towards normal esophageal epithelial NE3 cells and human skin
keratinocyte HaCaT cells. On the basis of these evidences, d-glucose modified gelatin/collagen matrix
nanoparticles containing C. officinalis powder might be proposed as a safer alternative vehicle for anticancer
treatments.